Continued theoretical studies in population genetics, molecular evolution, and genome mapping have led to new analytical methods and the development of statistics and computer programs. In population genetics and molecular evolution, the focus has been on recombination and linkage disequilibrium. The theoretical studies are the basis for our evolutionary analysis and phylogenetic reconstruction of multiple alleles sampled from closely related species. We are applying these analyses to the major histocompatibility complex, where these issues are critical due to the extremely high levels of polymorphism, some of which appears to pre-date many major speciation events. Our studies of genome mapping have concentrated on comparative mapping and the human cytogenetic map. In comparative mapping, we have devised analytical methods of comparison that are useful for prediction of relative map locations between species and for contrasting the relative evolution among chromosomes and among species. These have been applied to existing data sets for humans and mice, as well as a range of 20 other mammals. Also, we are currently working on organizing comparative mapping data in a way that will expedite comparative mapping. Our work with the human cytogenetic map continues in three overlapping areas. Computer programs for representing and manipulating cytogenetic maps will be augmented by analytical methods for improving the actual data contained in the maps. We will extend our earlier work on using gene order information from linkage maps to refine cytogenetic localizations, and apply it to relevant data sets.